Induction of intracellular interleukin-1 beta signals via type II interleukin-1 receptor in human gingival fibroblasts

The type II interleukin-1 receptor (IL-1RII) has been thought to be incapab le of transducing signals to cells because of its short intracellular domai n, while type I IL-1 receptor (IL-1RI) does transduce signals. Since over-e xpression of IL-1RII has been demonstrated to inhibit cytokine production i n the fibroblastic cell line, it has been proposed to use IL-1RII to preven t IL-1-induced inflammation in connective tissue. In this study, trace amou nts of IL-1RII mRNA expression were detected in human gingival fibroblasts (HGFs), which are affected by cytokines in inflammatory periodontal disease . Cloning of the cDNA encoding IL-1RII expressed in HGFs revealed 3 amino a cid substitutions in the extracellular domain, when compared with the 408 r esidues predicted from human B-cells. Over-expression of IL-1RII on HGFs by gene transfer down-regulated the expression of IL-1 beta mRNA and IL-6 mRN A in response to IL-1 beta stimulation, while the expression of IL-8 mRNA w as not affected. In the IL-1RII-transfected HGFs, phosphorylation of 25- an d 74-kDa proteins was up-regulated upon IL-1 beta stimulation in the transf ected HGFs. The phosphorylation of these proteins was suppressed by the add ition of a neutralizing antibody against IL-1RII. These results suggest tha t the IL-1RII may regulate HGFs expression of cytokine mRNA upon IL-1 beta stimulation, possibly by altering the IL-1RI-dependent signals.